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Clinical Trials/NCT03422224
NCT03422224RecruitingNot Applicable

Alloreactive t Cell Repertoire in Kidney Transplantation Recipients

Medical University of Vienna1 site in 1 country50 target enrollmentStarted: July 1, 2017Last updated:
Conditions

Trial Snapshot

Phase
Not Applicable
Status
Recruiting
Enrollment
50
Locations
1
Primary Endpoint
Rejection

Study Overview

Brief Summary

In this study, the investigators will establish a workflow to generate unique patterns of the donor-reactive T cell repertoire using mixed lymphocyte reactions to select alloreactive T cell clones prior to transplantation Tissue infiltrating as well as blood bound T cells will be characterized based on:

  1. Identification of donor-specific T cell receptor sequences pre- and post-transplant by in vitro expansion to determine unique patterns
  2. Quantification and comparison of donor-specific T cell clones in kidney biopsy and blood samples.
  3. Analysis of the TCR repertoire diversities derived from kidney biopsy and blood samples and association of repertoire diversities with the histomorphological phenotype of T cell mediated rejection.
  4. Identification of T cell subtypes within the donor-reactive population. The investigators specifically hypothesize that highly expanded donor-reactive T cell clones in both kidney tissue and blood samples at time of indication biopsy are associated with the histological phenotype of acute T cell mediated rejection. The investigators have previously shown that there is a strong correlation between highly expanded tissue-resident T cell clones and the repertoire found in periphery blood samples. To trace and quantify donor reactive T cells the investigators will apply a truly quantitative approach for immune repertoire profiling based on high- throughput sequencing. The investigators ultimate goal is to develop a diagnostic tool to assess alloreactive cellular immunoresponses based on peripheral blood samples.

Detailed Description

Kidney transplant recipients receiving a non lymphodepletional induction therapy at the investigators center will be included in this study.

Alloreactive T cells are defined prior to transplantation via a mixed lymphocyte reaction of donor and recipient PBMC's.

Following transplantation PBMC's will be sampled at management (3 and 12 months) and for-cause biopsies and fifteen patients with histological proven acute T cell mediated rejection will be compared to 15 patients without histopathological signs of alloimmune response in time matched for-cause biopsies.

T cell receptor beta chains of T cells found in the circulation and the allograft biopsy will be sequenced via Next generation sequencing.

Abundance of alloreactive T cells of the overall repertoire pre-and post-transplant and their presence in the allograft will be assessed.

Study Design

Study Type
Observational
Observational Model
Case Control
Time Perspective
Prospective

Eligibility Criteria

Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Kidney transplantation in our center

Exclusion Criteria

  • Donor not evaluated by our center

Outcomes

Primary Outcomes

Rejection

Time Frame: 12 months

biopsy proven rejection

Secondary Outcomes

No secondary outcomes reported

Investigators

Sponsor Class
Other
Responsible Party
Principal Investigator
Principal Investigator

Rainer Oberbauer

Prof. Dr

Medical University of Vienna

Study Sites (1)

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